The high incidence of alcohol abuse that occurs in patients with chronic pain underscores the importance of continued research towards effective treatments for both pain and alcohol use disorders. It has been found in animal models that chronic alcohol exposure can drive adaptations in the brain, which drive increased pain- related behaviors. Our long-term goal is to understand how chronic alcohol exposure can alter the neuronal circuits that regulate pain-related behavior in order to develop more effective approaches to treat alcohol induced pain. One region of particular interest for these studies is the periaqueductal gray (PAG). We have previously shown that a subpopulation of dopamine neurons in the ventrolateral PAG (PAGDA) are activated by acute alcohol and activation of these same neurons induces an anti-nociceptive effect in the hot-plate test. Furthermore, in our preliminary data, we found that activation of the outputs to the bed nucleus of the stria terminalis (BNST) could replicate this anti-nociceptive effect. These findings are noteworthy, as they identify a novel ascending anti-nociceptive pathway (PAGDA to BNST) distinct from the well-characterized descending anti-nociceptive pathway (PAG to Medulla). In keeping with the critical role of the PAGDA to BNST pathway, we found that viral deletion of CRF from the BNST can alter pain related behaviors. In addition, we have found that intermittent alcohol drinking can drive changes in pain-related behavior in mice. Taken together, these studies support the testable hypothesis that intermittent alcohol drinking drives alterations in pain related behavior, in part through disruptions in the PAGDA to BNST pathway, and that in vivo activation of this pathway can ameliorate alcohol- induced hyperalgesia.